Abstract
Background/Aims With over 300 FDA-regulated clinical trials currently open at Kaiser Permanente Northern California (KPNC), the need for a quality-based systems approach for managing clinical trials and preparing for FDA audit of these trials is paramount. Over the past five years, the FDA’s Division of Bioresearch Monitoring (BIMO) has conducted, on average, 325 to 350 inspections of medical device clinical trials each year. In 2011, FDA issued warning letters to Sponsors, IRBs, and Clinical Investigators, citing numerous GCP violations involving pharmaceutical trials. Non-compliance findings ran the gamut; from violations related to required regulatory submissions to deviations from written procedures, and failures to maintain study documents. This presentation will: (1) discuss the triggers and types of FDA audit and the procedures necessary to prepare KP investigators and sites for a successful audit, and (2) discuss the approaches to ensure GCP and audit-readiness at all times. A case study of a routine BIMO audit of a KPNC study site participating in an investigational device trial will be presented.
Methods Prior to an FDA audit, a member of the Comprehensive Clinical Research Unit (CCRU) of the KPNC Division of Research routinely conducts a comprehensive site gap analysis to determine compliance issues or deficiencies in clinical research practices. A gap analysis includes reviewing records and procedures concerning interactions with the IRB; reviewing records and procedures concerning test article accountability, Adverse Event (AE) reporting, human subject protections, subject enrollment criteria; reviewing the facility and equipment; and verifying that data collected in Case Report Forms are supported by source documents.
Results Prior to the device BIMO audit at the KPNC site, we conducted a gap analysis of 100% of patient and research records to determine research compliance. The gap analysis allowed the study team to identify and correct deficiencies that would have otherwise increased the site’s risk for unfavorable findings, and allowed the site to implement preventive actions to sustain high-level compliance. The site passed the audit successfully without a single citation from the FDA.
Conclusions Conducting a comprehensive pre-audit gap analysis and a quality-based systems approach to maintain optimal GCP compliance are essential to a successful audit.
